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Universal vaccine against respiratory syncytial virus A and B subtypes

View Article: PubMed Central - PubMed

ABSTRACT

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131–230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology. We immunized mice with GcfAB plus cholera toxin as a mucosal adjuvant via intranasal (IN) or sublingual (SL) routes. The IN group showed higher levels of RSV G-specific antibody responses, including serum IgG and mucosal IgA, compared with the SL group. On the contrary, more vigorous RSV G-specific CD4+ T-cell responses were elicited in the SL group than in the IN group after RSV-A but not RSV-B viral challenge. Furthermore, the SL group showed more pulmonary eosinophil recruitment and body weight loss than did the IN group after RSV-A challenge. Both IN and SL immunization with GcfAB provided potential protection against both subtypes of infections. Together, these results suggest that vaccination with GcfAB via an IN route could be a universal vaccine regimen preventing both RSV A and B infections.

No MeSH data available.


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RSV B-specific Th1 and Th17-cell responses in GcfAB-immune mice after RSV B challenge.After RSV B (KR/B/10-12) challenge, all mice (n = 4/group) were sacrificed and lung mononuclear cells were isolated 5 days post-infection. Lung lymphocytes were stimulated and were analyzed as the same manner as in Fig 4. (A) CD3+ and CD4+ cells are shown in the dot plots, (B) and the percentage of such cells is represented as the frequency of RSV G-specific IFN-γ+ and IL-17A+ CD4 T cells. Data are represented in mean ± SD (n = 4/group). Significant differences are marked with a hash tag (#, p < 0.05).
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pone.0175384.g005: RSV B-specific Th1 and Th17-cell responses in GcfAB-immune mice after RSV B challenge.After RSV B (KR/B/10-12) challenge, all mice (n = 4/group) were sacrificed and lung mononuclear cells were isolated 5 days post-infection. Lung lymphocytes were stimulated and were analyzed as the same manner as in Fig 4. (A) CD3+ and CD4+ cells are shown in the dot plots, (B) and the percentage of such cells is represented as the frequency of RSV G-specific IFN-γ+ and IL-17A+ CD4 T cells. Data are represented in mean ± SD (n = 4/group). Significant differences are marked with a hash tag (#, p < 0.05).

Mentions: Next, in order to investigate whether GcfAB elicits CD4 T-cell responses upon RSV B subtype infection, GcfAB-immune mice were challenged with an RSV B (KR/B/10-12) clinical isolate with the same 131–230 amino acid sequence as GcfB. Five days post-challenge, GcfAB-immune mice were sacrificed and lung lymphocytes were stimulated with the G/183-195 peptide of the RSV B subtype (KSICKTIPSNKPKKK) which corresponds to the CD4+ T-cell epitope of GcfA. After 5 hours, the levels of IFN-γ- and IL-17A-expressing CD4 T cells were measured by flow cytometry (Fig 5A) in the same manner as in Fig 4. Both IFN-γ- and IL-17A-expressing cells were significantly fewer following RSV B G peptide stimulation (Fig 5B) as compared to those seen following RSV A2 G peptide stimulation after RSV A challenge (Fig 4B). These results indicate that a.a. residues 183–195 of the RSV B G protein do not play roles as CD4+ T-cell epitopes, as previously reported [29]. Consequently, CD4 T-cell responses for the RSV B subtype were not found in our study.


Universal vaccine against respiratory syncytial virus A and B subtypes
RSV B-specific Th1 and Th17-cell responses in GcfAB-immune mice after RSV B challenge.After RSV B (KR/B/10-12) challenge, all mice (n = 4/group) were sacrificed and lung mononuclear cells were isolated 5 days post-infection. Lung lymphocytes were stimulated and were analyzed as the same manner as in Fig 4. (A) CD3+ and CD4+ cells are shown in the dot plots, (B) and the percentage of such cells is represented as the frequency of RSV G-specific IFN-γ+ and IL-17A+ CD4 T cells. Data are represented in mean ± SD (n = 4/group). Significant differences are marked with a hash tag (#, p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5383302&req=5

pone.0175384.g005: RSV B-specific Th1 and Th17-cell responses in GcfAB-immune mice after RSV B challenge.After RSV B (KR/B/10-12) challenge, all mice (n = 4/group) were sacrificed and lung mononuclear cells were isolated 5 days post-infection. Lung lymphocytes were stimulated and were analyzed as the same manner as in Fig 4. (A) CD3+ and CD4+ cells are shown in the dot plots, (B) and the percentage of such cells is represented as the frequency of RSV G-specific IFN-γ+ and IL-17A+ CD4 T cells. Data are represented in mean ± SD (n = 4/group). Significant differences are marked with a hash tag (#, p < 0.05).
Mentions: Next, in order to investigate whether GcfAB elicits CD4 T-cell responses upon RSV B subtype infection, GcfAB-immune mice were challenged with an RSV B (KR/B/10-12) clinical isolate with the same 131–230 amino acid sequence as GcfB. Five days post-challenge, GcfAB-immune mice were sacrificed and lung lymphocytes were stimulated with the G/183-195 peptide of the RSV B subtype (KSICKTIPSNKPKKK) which corresponds to the CD4+ T-cell epitope of GcfA. After 5 hours, the levels of IFN-γ- and IL-17A-expressing CD4 T cells were measured by flow cytometry (Fig 5A) in the same manner as in Fig 4. Both IFN-γ- and IL-17A-expressing cells were significantly fewer following RSV B G peptide stimulation (Fig 5B) as compared to those seen following RSV A2 G peptide stimulation after RSV A challenge (Fig 4B). These results indicate that a.a. residues 183–195 of the RSV B G protein do not play roles as CD4+ T-cell epitopes, as previously reported [29]. Consequently, CD4 T-cell responses for the RSV B subtype were not found in our study.

View Article: PubMed Central - PubMed

ABSTRACT

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131&ndash;230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology. We immunized mice with GcfAB plus cholera toxin as a mucosal adjuvant via intranasal (IN) or sublingual (SL) routes. The IN group showed higher levels of RSV G-specific antibody responses, including serum IgG and mucosal IgA, compared with the SL group. On the contrary, more vigorous RSV G-specific CD4+ T-cell responses were elicited in the SL group than in the IN group after RSV-A but not RSV-B viral challenge. Furthermore, the SL group showed more pulmonary eosinophil recruitment and body weight loss than did the IN group after RSV-A challenge. Both IN and SL immunization with GcfAB provided potential protection against both subtypes of infections. Together, these results suggest that vaccination with GcfAB via an IN route could be a universal vaccine regimen preventing both RSV A and B infections.

No MeSH data available.


Related in: MedlinePlus